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• W4387340287 endingPage "213649" @default.
• W4387340287 startingPage "213649" @default.
• W4387340287 abstract "The use of nanoparticle (NP) delivery systems in cancer treatment has received significant interest, however use of such systems in delivery of cytotoxic chemotherapy agents can be limited by low encapsulation efficiency and burst release of the cytotoxin, as well issues with throughput and reproducibility during the fabrication of drug-loaded NPs. In this study, we used a hydrodynamic flow-focusing microfluidic system to successfully produce poly(lactic-co-glycolic acid) (PLGA) NPs. The physico-chemical properties of PLGA NPs were controlled by changing the manufacturing parameters, such as flow rate ratio, total flow rate, PLGA and surfactant concentration. The NAMPT inhibitor-polymer conjugate, hydroxyl-FK866-PLGA, was synthesized and used to fabricate hydroxyl-FK866-PLGA NPs for the formulation of localized delivery systems able to release low doses of cytotoxins and enhance the efficacy of NAMPT inhibitors. Hydroxyl-FK866-PLGA NPs were prepared with optimized fabrication parameters, having average Z-size of 128 ± 8 nm (PDI < 0.2), ζ-potential of -14.8 ± 5.3 mV and high encapsulation efficiency (98.6 ± 5.8 %). The pH-dependent release of hydroxyl-FK866 was monitored over time in conditions mimicking the normal (pH 7.4) and inflamed/tumor (pH 6.4) microenvironments, observing a sustained release pattern (over two months) without any initial burst release. Finally, toxicity of hydroxyl-FK866-PLGA NPs were tested in selected human cell lines, the human leukemia monocytic cell line (THP-1), and the human triple negative breast cancer cell line (MDA-MB-231). Our work suggests that microfluidic systems are a promising technology for a rapid and efficient manufacturing of PLGA-based NPs for the controlled release of cytotoxins. Moreover, the use of drug-polymer conjugates is an effective approach for the manufacturing of polymeric NPs enabling high encapsulation efficiency and a prolonged and sustained pH-dependent drug release." @default.
• W4387340287 created "2023-10-05" @default.
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• W4387340287 date "2023-11-01" @default.
• W4387340287 modified "2023-10-13" @default.
• W4387340287 title "Design of PLGA nanoparticles for sustained release of hydroxyl-FK866 by microfluidics" @default.
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• W4387340287 doi "https://doi.org/10.1016/j.bioadv.2023.213649" @default.
• W4387340287 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37820459" @default.
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